Novel p104 protein regulates cell proliferation through PI3K inhibition and p27(Kip1) expression.

The protein p104 was first isolated as a binding partner of the Src homology domain of phospholipase Cgamma1, and has been shown to associate with p85alpha, Grb2. The ectopic expression of p104 reduced cellular growth rate, which was also achieved with the overexpression of only the proline-rich region of p104. The proline-rich region of p104 has been found to inhibit the colony formation of platelet-derived growth factor BB-stimulated NIH3T3 cells and MCF7 cancer cells on soft agar. Mutagenesis analysis showed that the second and third proline-rich regions are essential for growth control, as well as for interaction with p85alpha. Overexpression of p104 increased the level of the cyclin-dependent kinase inhibitor, p27(Kip1), and inhibited the activity of phosphoinositide 3-kinase (PI3K). In summary, p104 interacts with p85alpha and is involved in the regulation of p27(Kip1) expression for the reduction of cellular proliferation.